Millennium Evening at the White House:
Informatics Meets Genomics

THE WHITE HOUSE

Office of the Press Secretary

East Room

October 12, 1999
7:35 p.m. EDT

MRS. CLINTON: Good evening, and welcome to the White House. Imagine for a moment that it is the year 2030. You could instantly teleconference with your children any time, anywhere, if they will accept the teleconference. (Laughter) You could speak into a computer and have your words instantly translated into any language. If you're paralyzed in an accident, you can regain your mobility. And if you lose your sight, you will regain it.

Well, welcome to the future, and to the 8th Millennium Evening at the White House. Tonight we will explore the explosion of information technology and genetic research, and how they are combining to shape how we live, learn, and think in the next century.

I'd like to thank our sponsor, the National Endowment for the Humanities, which every day helps create informed citizens and public debates like this one. And I'd like to recognize its chairman, Bill Ferris, for his work.

I also want to recognize the many members of the President's administration who are here, including Secretary Donna Shalala; Secretary Dick Riley; NIH Director Harold Varmus; NASA Administrator Dan Goldin; National Science Foundation Director Rita Colwell; Director of the NIH Human Genome Project Francis Collins; and the President's Science Advisor Neal Lane.

I also want to thank the Library of Congress and the Smithsonian for the exhibits in the foyer.

We're actually using some of the science that we are celebrating tonight. People from all over the world can participate in this event via satellite and over the Internet, thanks to John Shoemaker and the entire team at Sun Microsystems. And you will watch video all evening on these plasma screens, thanks to Pioneer New Technologies.

For the past two years, we have used these Millennium Evenings to showcase the art, culture, history and science that define us as a people and as a nation. When Professor Bernard Bailyn lectured, this room was filled with historians. When Wynton Marsalis played here, it was filled with musicians. And it's safe to say tonight that we have the largest gathering of geneticists and IT experts ever assembled together in the East Room of the White House. (Laughter)

These lectures are part of the work of the White House Millennium Council that the President and I started to encourage all Americans to use this unique moment in time to honor the past and imagine the future. And that is exactly what we will do this evening.

If we pick up any magazine or newspaper these days, these are the kinds of headlines we're likely to find: "Twins Unlocking the Secret of Identity;" "How the Wireless World Will Change Your Life;" "DNA Mapping: Light at the End of the Tunnel."

We are on the brink of discoveries that are astonishing in their complexity and implications for human life in the decades ahead. But they didn't happen overnight. These revolutions have been driven by our American quest for knowledge and discovery -- and the willingness of both the public and private sectors to invest in the necessary research.

More than 200 years ago, before we had even drafted a Constitution, our second President, John Adams, created the American Academy of Arts and Sciences to, in their words, "cultivate every art and science which may tend to advance the interests, honor, dignity and happiness of a free, independent and virtuous people."

That same spirit is what drives us to go to the next generation Internet and to find the 3 billion letters of genetic instructions to the human body. And it must continue to drive us as we educate and inspire Americans to understand these breakthroughs, and continue investing in science and technology research well before we know whether it has any commercial applications.

After all, when Vint Cerf and Robert Kahn found a way for computers to talk to one another, they certainly didn't imagine E-Bay or Amazon.com. (Laughter)

But, now, even in the face of these great breakthroughs there are many who rightly worry that our science is developing faster than our ability to understand its implications. Because behind each of the headlines we read we find not only great possibilities, but also profound ethical questions that we must answer together.

As we gather more information -- whether it is commercial transactions posted on the Internet or genetic information collected by doctors -- who owns that information? How will we protect our privacy? How will we make sure that knowledge about our genes is used to heal us, not deny us health insurance or jobs? What do justice and equality mean in a digital age?

In one of his short stories, Ray Bradbury's vision of the year 2030 has some similarities to the one I started with tonight: the windows wash themselves, breakfast cooks itself, and a voice machine reminds you of birthdays, anniversaries and bills to be paid, which is especially handy as one gets older. (Laughter) There's only one big difference: There are no people. The population has been completely wiped out and all that's left are machines.

Standing here with only 80 days left until the year 2000, we have a chance to imagine and create a very different future. One in which the revolutions in information and biology benefit, rather than eclipse, our humanity; where our ethics keep pace with our science; where our investments in science dramatically improve not only how long we live, but how well we live. Because unlike science fiction, how this story ends is in all of our hands.

So I want to thank you for coming this evening. And we have invited two distinguished scientists to help us understand that promises and perils of information tm prestigious universities; and both are visionaries.

First, Dr. Vinton Cerf will give us a quick overview of the growth and future of the Internet. Then Dr. Eric Lander will tell us about the revolution in genetics and where it is leading us.

Dr. Lander actually started his career as a mathematician. As a high school student, he even won a place on the U.S. team to the International Mathematical Olympiad held in East Germany. This was at the height of the Cold War. But when his team and the Russian math team met at the competitions, they hit it off. They spent evenings together, tossing water balloons down on to the streets of East Germany in defiance. And he has been bringing people and disciplines together ever since. (Laughter)

He's built bridges to public policy, and by contributing his time, has really added to the public debate as an NIH advisor. He's also the founder of Millennium Pharmaceuticals, and now he's building bridges between genetic discoveries and their potential to improve our lives as the Director of the Whitehead Institute/MIT Center for Genome Research.

Now, I'm told that Dr. Cerf, one of the fathers of the Internet, also got his start in high school. Back then, he and his best friend got permission to use a computer at UCLA. When the building was locked on weekends, they would simply climb up to an open third-story window. The machine was a size of a refrigerator and had the computing power of today's hand-held calculators. But he was consumed by the possibility computers held, and has been scaling wall after wall ever since then to fulfill it. (Laughter)

As the Advanced Research Projects Agency of the Department of Defense, he helped to develop the procedures or protocols that computers use to communicate with each other. And he's chairing the new Internet Societal Task Force that is helping to make the Internet accessible to everyone.

He's a senior Vice President at MCI WorldCom for Internet Architecture and Technology. And I think that every parent should take heart that people who throw water balloons and scale to third-floor windows do have a future -- (Laughter) -- that will in one way or another be redemptive.

DR. CERF: I didn't know you were going to dig up that story about our high school escapades. Let me thank you, Mrs. Clinton, for introducing me not as an "extinguished" scientist. I appreciate that. One wonders, as time goes on.

Well, Mr. President, Mrs. Clinton, ladies and gentlemen, Internet is the consequence of the work of many people. In 1997, President Clinton recognized the contribution that my partner, Bob Kahn, and I made when he awarded us both the National Medal of Technology for the design of the architecture and communication protocols of the Internet. Bob is here tonight, and I'd like to acknowledge his creative leadership. Bob, would you stand up for a minute? (Applause)

I also want to acknowledge the contributions of President Clinton and Vice President Gore in shaping the administration policy, and in legislation supporting research and development that's needed to make Internet a global reality, and to continue its astonishing evolution.

The 19th century invention of telegraph and telephone systems dramatically changed the way in which people could interact with each other. Dial-tone has become the symbol of voice communication around the world.

During the 20th century, we learned that computers could usefully talk to each other, too, using packet switching as their data tone. You can think of packet switching as a kind of electronic postal service in which everything that moves through the system is like an electronic postcard that's forwarded from one computer to another until it reaches its destination. The special computers that perform this function are called routers, and you can think of them as forming many different bucket brigades spanning continents and oceans, moving buckets full of electronic postcards from one router to another, until the postcards reach their destination.

Each bucket brigade is a network and there are hundreds of thousands of them in the world, connected together to make up the network of networks that we call the Internet. Everything we know about postcards applies to these packets of the Internet -- they can get lost, they can be delivered out of order, and they can be delayed by varying amounts in the net. They can even be duplicated by the net, which is not something that the U.S. Postal Service offers as a service. (Laughter) Of course, packet switching is about a billion times faster than the Postal Service or bucket brigade would be.

Now, the procedures by which computers communicate with each other and the formats of the electronic postcards that they send are called protocols. And the most basic protocol on the Internet is called the Internet protocol, or IP for short. Now, to make the Internet service reliable -- which it is not using just those postcards that I described -- you have to add other layers of protocol on top. One of the most important of these is called TCP; it stands for transmission control protocol -- and you're getting your dose of geek vocabulary tonight.

This takes care of resending to recover from a lost postcard or a lost package, or putting the package back in order if they have been received out of order. One sometimes hears the term, "TCPIP" with reference to the Internet. Those are the two fundamental protocols of the network.

Now, there's another way of thinking about the power of interconnecting computers through networks, and that's to think about the way we use electrical power generation and distribution and fractional horsepower motors in our daily lives. Think about how many little modems are working for you every day to keep your ice cream from melting, to start the car and to keep the clock turning. That's the kind of thing that we relied on in our mechanical world.

Well, computers are like fractional horsepower motors, and information is like electricity. Information flows through networks and feeds computers in a fashion that's very similar to the way electricity flows through the electrical power network and runs motors. During the industrial revolution, we learned to put motors to work to magnify human and animal muscle power. In our information age, we're learning to magnify brainpower by putting computing power to work wherever we need it to work with information for us whenever we need help.

Filled with software, computers allow us to use them as infinitely flexible tools. Networked together, they allow us to generate, exchange, share and manipulate information in uncountable ways.

There are about 60 million computers on the Internet today serving about 180 million users. Internet service is found in varying degrees in over 200 countries and territories. Now, for comparison, today's telephone system has 950 million telephone lines and about 3 billion users. So Internet, despite all the hype, has a long way to go. But, by the end of the year 2000, I estimate there will be at least 300 million users on the network. And a straightforward projection of the growth of the Internet brings it to nearly the size of today's telephone system by 2006. Indeed, the Internet may have become the telephone network by that time, if our ability to do Internet telephony works out as well as some of us hope it will.

Some people are confused about the relationship between the World Wide Web and the Internet. Internet provides the plumbing to transport data for a variety of applications, and the World Wide Web is one of them. But there are others, including electronic mail, Internet telephony, Internet radio and television -- which is how we're multicasting this event tonight over the net -- group interactive games, collaboration tools, and a host of other applications.

Today, almost 8,000 radio stations put their audio on the Internet. And on the net today there's also a little bit of video, and a certain amount of telephony -- speaking of which, my colleagues and I back in the 1970s did experiments with voice on the Internet. But we had so little capacity in the system that we had to compress the voice -- to shrink it down into a smaller number of bits per second. When you talk on the telephone net today, you're using 64,000 bits per second of capacity to deliver the sound. But on this very small little Internet in the '70s, we had to squeeze it down to 1,800 bits per second. It worked very well, except one little side effect -- it made everyone sound like they were Norwegian. (Laughter) But, apart from that, it worked very nicely. (Laughter)

Mobile access is also emerging, with wireless local area networks, digital cellular telephones and mobile data radios which allow your computer to connect to the Internet over the radio now.

Now, in addition to conventional desktop and laptop computers, there are many other devices that are becoming Internet-enabled -- things like Internet televisions, two-way radio pagers like this one that can do e-mail on the Internet, over the air. You can see, it has a keyboard that is suitable for people who are three inches tall -- (Laughter) -- but, apart from that, it's a minor detail, everything else works.

Cellular phones today can surf the World Wide Web. You'll be able to program your VCR by pulling up a pay on the web, clicking on the programs that you want to record. And the instructions to do that will go through the net to your VCR. This beats trying to find an 11-year-old to help you do it. (Laughter) And, by the way, once the VCR is on the net, it can find out what time it is and get rid of the flashing 12:00 that's on -- (Laughter)

Indeed, many kitchen appliances, such as the refrigerator and the washing machine may be on line in the future. And there are some pretty funny scenarios that result from that. For example, the bathroom scale that sends your weight to the doctor and that becomes part of the medical record. Unfortunately, the same information may get to your refrigerator -- (Laughter) -- which will refuse to open because it knows you're on a diet. (Laughter) The refrigerator could scan the bar codes on items that were put into it, so it could keep track of what was in the refrigerator and how old it is. So you might get an e-mail from your refrigerator warning you the milk is three weeks old -- (Laughter) -- and it's going to crawl out on its own if you don't do something about it. It might even compose a potential shopping list for you based on what it knows you've bought in the past.

Well, the Internet's also playing a major role in facilitating electronic commerce. By 2003, electronic commerce of all kinds may reach somewhere between $1.8 and $3.2 trillion in value. That's between five and ten percent of the world's economy. So it's no surprise that there's a lot of interest in what the Internet is doing to us in terms of legal issues and personal issues.

Internet is going to get into everything. Here's an example of a web-server that fits on a single chip. In fact, the chip is smaller than the plug that connects the server into the Internet. We'll be able to Internet-enable almost anything. And Internet is going everywhere. Here, you see two young men putting up an Internet sight in Kihihi, Uganda, in a village far, far away.

Well, a vast array of public issues arise with the use of the Internet. As the Internet begins to carry all of its predecessor media -- television, radio, print media and telephony -- questions about the protection of intellectual property and regulation become increasingly important. Taxation of transactions on the Internet is yet another major topic, because Internet is global and any effort to tax its transactions will require global agreement on suitable practices and procedures.

The question of control of content on the net is another frequent topic of debate highlighting the tension between freedom of speech between adults, on the one hand, and the protection of young people who might not need to be exposed to some of that information while they're on the net, on the other. And similarly, citizens are interested in protecting their privacy as they use the Internet.

Well now, let's look to a more distant future. My colleagues at the Jet Propulsion Laboratory and I have been working on an extension of the Internet to outer space. As we all recall, JPL has been commissioned by NASA to launch a series of missions to Mars every 26 months. Last year, we all shared in the excitement of seeing dramatic photographs relayed from Mars by the rover of the Pathfinder mission.

A year or so ago, several of us interested in the use of Internet in space began to work on the use of Internet to support future communication needs of robotic and manned missions in the exploration of space. This is really a different environment. It takes 80 minutes for a signal to go from Earth to Mars and back again, for example, in the worst case.

We're designing an interplanetary backbone which we hope to be functioning between the Earth and Mars as early as 2008. NASA's Administrator, Dan Goldin, often speaks of Internet-enabled Mars, as a way of capturing this notion. And by 2040, we hope a stable interplanetary backbone can be established between the planets.

Meanwhile, back on Earth, the link between the information of the Internet and the human genome is most vividly illustrated by genetic research which uses information technology to determine and analyze the 3 billion pieces of information that make up the complete DNA sequence of a human being. And speaking of biotechnology, I believe it will be routine in the 21st century to interconnect our nervous system with electronic equipment.

The best example of this, using today's technology, is the cochlear implant. The implant bypasses the mechanics of the inner ear to directly interface to the auditory nerve. A speech processor, a computer about the size of a pager, is connected to a sound source, such as a microphone, and delivers stimuli to the implant which directly signals the auditory nerve. This is a direct computer nervous system interconnection.

My wife, Sigrid, who is here with us in the audience, lost her hearing at the age of three, and she was profoundly deaf for 50 years. Three years ago, she learned enough about cochlear implants through the Internet to determine she might be a candidate for an implant. After a positive evaluation, she had the implant done as an out-patient operation at Johns Hopkins University, and after the surgery had healed, she returned to be activated. (Laughter)

About 20 minutes after this was done, she called me on the telephone -- and for the first time we had a telephone conversation -- for the first time in our 30 years of marriage. Now, we have a big problem -- we have a 56-year-old teenager in the house. (Laughter)

She uses the telephone regularly, she listens to radio and television. She carries a variety of patch cables that allow her to connect her computer speech processor to any source of sound. And on airplane trips she just plugs into the arm rest, she doesn't have to wait for the headphones. (Laughter)

Sigrid's surgeon, John Neparco (phonetic), is here tonight, too. John, would you stand up for a moment to be recognized. (Applause)

Sigrid, can you stand up and show us what that speech processor actually looks like? We can get the camera on this so that we should be able to see it on the screen in a minute here. There we go. Hold it still. And, Sigrid, could you tell us what it was like to suddenly regain your hearing after 50 years of silence?

MRS. CERF: It's been a party every day. It's been such fun -- I'm going out and hearing the birds, rushing to the phone to get telemarketing calls -- (Laughter) --

DR. CERF: I like the one where she listened to the AT&T spiel all the way to the end with a big smile and then said, "No, Vint the Cerf works for MCI WorldCom, we don't think we'll switch." (Laughter)

MRS. CERF: A peak experience is being able to hear and recognize the voices of President and Mrs. Clinton on the radio.

DR. CERF: That's neat. Thank you, Sigrid. (Applause)

Well, to sum up, Internet is becoming and will be central to human communication in the decades ahead. It enables interaction among cultures and societies on an unprecedented scale and among individuals and groups with a facility unknown in the past. In simple terms, there is an Internet in your future; resistance is futile. Thank you very much. (Laughter and applause)

MRS. CLINTON: Thank you very much, Vint, and thank you, Sigrid, for being part of this evening and for that demonstration.

Vint told us about how one information system is changing our lives and foreshadowed what will happen when it becomes even more possible to be combined with biotechnology. Now, to explain the information system known as the genome is Dr. Eric Lander. (Applause)

DR. LANDER: Thank you, Mrs. Clinton. I want to thank both the President and the First Lady for the invitation to speak here tonight. We are in the midst of one of the most remarkable revolutions in the history of mankind. The revolution was sparked by scientific curiosity about life, but its consequences would be so far-reaching as to touch every aspect of society. It is an information revolution, unlocking databases of human heredity and evolutionary history. It is a medical revolution, holding the prospect that our children's children will never die of cancer. And it is an intellectual revolution that may reshape, for better of for worse, our notions of human potential.

I refer, of course, to the revolution in genetics and genomics. Now, genetics is the study of biological diversity within a species. This is my favorite slide to illustrate the spectacular degree of diversity in our own species. It's a famous old picture of Wilt Chamberlain and Willie Shoemaker, and it shows the wonderful range of differences in such traits as height, weight, skin color.

But it's also emblematic for me of the many differences you don't see -- in susceptibility to heart disease, cancer, asthma and diabetes. All these differences are underlain by the action of multiple genes working together with environment. Now, to geneticists, such differences provide clues to the common biological mechanisms at work in all of us.

Genetics is quintessentially a child of the 20th century, born in the opening moments of this century. Of course, genetics does go back to Gregor Mendel's experiments with peas in 1865, but the work was largely ignored for 35 years. The real explosion began with three papers that rediscovered Mendel's work, the first of which appeared, as if keeping an appointment with history, in January 1900.

Now, at the start of the century, heredity was known to obey certain laws of transmission, but the hereditary information itself was a complete mystery. By quarter-century, heredity had a physical basis and a cellular structure -- the chromosomes. Chromosomes carried genes, whatever they were.

By mid-century, heredity had a molecular basis, in the form of deoxyribonucleic acid, DNA. It was clear that DNA somehow encoded the instructions to make every protein in our body: the hemoglobin in our blood, the keratin in our hair and the olfactory receptors with which we smell the fragrance of a spring day.

But, at the same time, it wasn't possible to read even a single gene. Now, three-quarters of the way through the century the recombinant DNA revolution burst on the scene, making it possible not only to read DNA sequences, but to isolate, modify and propagate genes, giving rise to the entire biotechnology industry.

And, now, as the century draws to a close, we're turning from the study of individual genes, genetics, to global views of all genes simultaneously -- genomics. We stand on the verge of having the complete sequence of the human genome, the complete 3 billion letters of genetic instructions for the human being, comprising roughly 100,000 genes.

Biologists will barely pause to mark this milestone, eager to race on to understand the information in the genome. But we should reflect a moment on the extraordinary journey, covering nearly 10 orders of magnitude, 10 powers of 10, in 10 decades.

Genetics has been largely the story of undirected, curiosity-driven research; arcane experiments about fruit fly families and bacterial defense mechanisms that paid huge dividends. The human genome project itself is the handiwork of thousands of scientists around the world in academia and in industry. But the American people and their government deserve special credit for having had the vision to launch this project more than 10 years ago, to invest in basic science when its benefits were still unclear. And I particularly want to acknowledge the leadership of Dr. Francis Collins, the Director of the Human Genome Project who is, of course, here tonight. (Applause)

Now, what will it mean to know the complete sequence of a genome? The right analogy, I believe, is with the discovery of chemistry's period table of the elements in the late 1800s. The recognition that all of matter could be described in terms of about 100 building blocks set the stage for chemistry in the 20th century. It rendered chemistry finite and predictable. It gave rise, on the one hand, to the chemical industry, among the other -- the theory of quantum mechanics.

Oh, genomics is now providing biology's periodic table. Not 100 elements, but 100,000 genes. Not rows and columns, but a more complex tree, showing the similarities amongst genes. The effect will be much the same -- to render biology finite. Scientists will know that every phenomenon must be explainable in terms of this measly list of 100,000 components. And just as the chemistry textbooks have the periodic table in the front cover of the textbook, so, too, will biology textbooks of the sequence of a human genome. Conveniently, one human genome fits snugly on a single CD rom.

How is genomics being used in medicine? First of all, to find genes for disease susceptibility. This can be done by correlating the inheritance patterns of a disease in families with the inheritance pattern of chromosomal regions, to home in on the location of a disease gene and discern its nature.

For cystic fibrosis, for example, the DNA sequence looked like this -- lots and lots of letters. And I call your attention to this tiny spot boxed in red, which I've blown up in the next slide there. That's right. The deletion of those three letters, C,T,T, encoding a single amino acid, phenylalanine, is the cause of cystic fibrosis in a vast majority of cases. About five people in this room carry that mutation. They're not, themselves, at risk, but they could have children with CF if they marry another carrier. And if on the way out of this room, everyone were to spit in a test tube, we would be able to analyze the DNA and call you back tomorrow and let you know which of you were carriers.

But there's more. If we toss the sequence of a cystic fibrosis gene into the computer and ask if the computer's ever seen anything like it before, the computer responds, yes, there are dozens of genes that are similar. They all reside at the cell's surface and they transport molecules. And that's before doing even a single experiment. We have a very good guess that the cystic fibrosis gene is a transporter, which indeed turns out to be right.

This shows clearly the power of transforming biology into an information-based science. Discoveries can be leveraged a hundred times over. The same approach has been used to identify genes from many diseases, including early onset breast cancer and colon cancer.

And here's a provocative example. There's a gene on chromosome 19 called apolipoprotein-E. It has three common alternative spellings in the population, called E-2, E-3 and E-4. Turns out, if you happen to have a double dose -- two copies -- of the E-4 spelling, you have an especially high risk of Alzheimer's disease later in life -- perhaps a 50 percent chance. About six people in this room have a double dose of E-4. And if, on the way out, you spit in the test tube, we can ring you back tomorrow and let you know if you're one of those people with high risk for Alzheimer's disease.

Do you want to know? I certainly don't. There's no therapy today for it. But at least the knowledge that apo-E is involved in the disease has propelled pharmaceutical companies to search for drugs that block its action.

Now, one consequence of the periodic table is that we can build detectors to follow how each gene is turned on and off under different conditions in the cell. By taking such global views, we can begin to infer the wiring diagram, the circuits and software of the cell, so to speak.

Everywhere, the focus is on mechanisms. We're beginning to understand diseases as mechanical processes, uncovering the cellular clockwork driving the mayhem of disease. Even aging is beginning to be understood as a programmed, molecular process -- raising the prospect that someday we may be able to slow its course.

Nowhere will the impact be greater than on cancer. Cancer treatment today consists largely of giving poisons to which rapidly dividing tumor cells are slightly more sensitive to normal cells. It's a blunt weapon, indeed. Now, for the first time, the features that distinguish cancer cells from normal cells are becoming clear. They suggest dozens of ways to specifically kill cancers. They go by arcane names like angiogenesis inhibitors and telomere blockers and antibody-mediated destruction. But these rational strategies will together provide us with multi-drug cocktails from which tumors can't escape. It will take patience and steady investment, but it's already clear that by the end of the next century cancer will no longer be the dread scourge that it is today.

And quite apart from its medical significance, the texture variation in the human genome holds great fascination. Any two human beings on this Earth are 99.9 percent identical at the DNA level -- only one difference in a thousand letters. So as you look to your neighbor to the left and to the right, you should appreciate how nearly identical you are. (Laughter)

On the other hand, one difference in a thousand letters in a genome of 3 billion letters still translates to 3 million differences between any two individuals. So if you look to your left and your right again, you can also revel in your absolute uniqueness. (Laughter)

DNA also teaches us about human history. Rare spelling differences in DNA can be used to trace human migrations. For example, scientists can recognize the descendants of chromosomes that ancient Phoenician traders left behind when they visited Italian seaports. DNA also tells us that we are a very young and closely related species. DNA variation reveals a human family tree in which all 6 billion humans on this Earth -- and I understand that last night at midnight, we officially passed 6 billion with a little baby born in Sarajevo -- all 6 billion humans on this Earth trace back to a small group of about 50,000 humans that lived in Africa a mere 7,000 generations ago, about 150,000 years ago.

The common genetic variance in the human population today largely traces back to that initial family population in Africa. And although the general public may imagine that there are sharp differences among racial and ethnic groups, most genetic variations are distributed across all groups.

Now, there is one crucial way in which my periodic table analogy breaks down. The chemical periodic table pertains to atoms and molecules. The biological periodic table speaks of people. The social consequences of genomics will be far-reaching, and I hope we'll have an opportunity to discuss them this evening.

Let me touch on one very briefly. In the short-term, the most pressing challenges will be to deal with the flood of genetic information. The key issue, I think, is privacy. We must protect the privacy of genetic information, so every citizen can get the information essential to their health without fear of repercussions. Should insurance companies have a right to know genetic information before providing health insurance? What about employers? The government? Even overzealous journalists?

There's been some progress in passing laws to prevent genetic discrimination in group health insurance, but there's currently no protection for individual health insurance, employment and general privacy. There's much work to be done.

Now, in the long-term, the most unsettling question will be whether we should ever re-engineer the human genome. Well-meaning enthusiasts are sure to begin proposing ways to improve the human genome -- to prevent cancer, slow aging, enhance memory. Concerning this last possibility, I'm sure you've all read that Princeton University, my alma mater, has expanded its educational mission. Biologists there are producing smarter mice by adding genes for certain neurotransmitter receptors.

But the notion that we can improve humans with a quick gene fix is, of course, naive. Human physiology is a delicate balance, and simplistic efforts are likely to do more harm than good. Just imagine the prospect of a product recall for a gene introduced into the human population that we later realized wasn't such a good idea. (Laughter)

Well, we can delay these prospects for a while by emphasizing our profound ignorance, but that's only a temporary solution. There will come a time when we can do such things safely, and we must discuss what we should do. Should we ever make a human being in someone's image, according to someone's plan? Would crossing this threshold turn human beings into products of manufacture? If we cross this threshold, will we ever return?

And then, finally, the most important issue will be the subtle ways in which genetic knowledge influences our own views of human potential. There is a risk that we may fall into a naive biological determinism, hewing to individuals as specified by their genes, limited by their genes.

This would be a colossal mistake. History is littered with supposedly scientific pronouncements about the limits of women, of African Americans, of Southern Europeans, of Asians, of Jews. Science has done a singularly poor job when it has sought to define limits on the human spirit, and on human potential.

Now, we need more nuanced ways to understand the role of genes and the range of human diversity. I'm particularly fond of this poster, from an exhibit at the Musee du Langue in Paris. It reads: "Tout parent, tout different." It can be translated two ways: all the same, all different; or all related, all different.

And this is, of course, a central theme -- perhaps the central theme in the American conversation. When Thomas Jefferson wrote the Declaration of Independence -- "We hold these truths to be self-evident that all men are created equal," -- the words, in fact, had a rather narrow meaning. But they have grown with the country, reinterpreted through the centuries by Elizabeth Katie Stanton at Seneca Falls, by Abraham Lincoln at Gettysburg, by Martin Luther King on the steps of the Lincoln Memorial. That fundamental credo that people must be judged for how they act, not for accidents at birth, will have even greater importance as we develop thousands of new ways in which we could, in principle, subdivide a people.

What a remarkable time. Genomics is opening breathtaking horizons in scientific understanding and medical progress. At the same time, it is presenting us with complex social choices. I know of no scientific field in which it is more exciting or more important for us all to imagine the future. Thank you very much. (Applause)

THE PRESIDENT: We have had many wonderful nights here, but I don't think I've ever been more stimulated by two talks in my life. Thank you, Dr. Cerf. Thank you Dr. Lander.

I would like to also say a word of appreciation to Hillary. I think that as our time here draws toward its close, it's clear that she has been, I believe, the most active and innovative First Lady since Eleanor Roosevelt, for, perhaps these Millennium Evenings will last longer in the imagination of America than virtually anything any of us have done, and I thank her for that. (Applause)

Also, being term-limited does have its compensations. Normally, at this time of year I'd be doing something else tonight. (Laughter) Yesterday, I called the Vice President to rub it in and describe what I would be doing tonight. (Laughter) And I was having a very good time turning the screw about how fascinating this was going to be. Finally he said, that's okay, you need to be there more than I do. (Laughter) The jokes about my technological and scientific limitations are legion around the White House. (Laughter)

So I have been thinking of all these questions -- do I really want a mouse smart enough to go to Princeton? (Laughter) Won't it be sad to have an Internet connection with Mars if there are no Martians to write to or e-mail us? (Laughter) I am glad to know that the total connection of the Internet to the nervous system of human beings is a little ways out there in the future. I had been under the impression that that had already occurred among all children under 15 in America. (Laughter)

This is an amazing set of topics. Let me say just one other thing. I really loved seeing, on a slightly sad note, I loved seeing that wonderful, famous picture of Wilt Chamberlain and Willie Shoemaker. Some of you may know the great Wilt Chamberlain passed away today, one of the greatest athletes of the 20th century. So I hope you will have him and his family and friends in your thoughts and prayers tonight.

This is a fitting thing for us to do in the White House, because innovations in communication and technology are a very important part of the history of this old place. In 1858, the first transatlantic telegraph transmission was received here in a message that Queen Victoria sent to President Buchanan. Later, the first telephone in Washington, D.C., was located in a room upstairs and we now have a replica of that telephone in the same room upstairs. The first mobile phone call to the moon was made here by President Nixon, 30 years ago. Even these Millennium Evenings have made their own history. This is where we held the first ever cybercast at the White House.

So I want to thank the speakers for building on all of this and telling us what we can look forward to in the future; and for reminding us that as we unlock age-old mysteries and make what we can think more possible to do, there are ways to do it that bring us together as a society.

So I would like to begin the questioning, if I might, with a question to Dr. Lander, because it bears on a great deal of the work we've done.

You talked about how we were 99.9 percent the same, but how if you looked at how many permutations there were in the one-tenth of a percent left we could still be very different. I think it's very interesting -- and I talk about this all the time -- that as we're on the age of this new millennium and we have these evenings and we imagine this future that you have sketched out to us, this is what we all like to think about, how exciting, how wonderful, how unbelievable it can be.

The biggest threat to that future is how many of us on this globe are still in the grip of the most primitive of human limitations -- the fear of the other, people who are different from us. And we see all over the world -- from Bosnia and Kosovo to the Middle East to Northern Ireland to the tribal wars in Africa, how easily the focus on our differences -- that one-tenth of one percent -- as what matters can lead first to fear, and then to hatred, and then, ultimately, to dehumanizing people who are different.

And it's very interesting -- as someone who grew up in the segregated South and lived with the whole terrible and, yet, beautiful struggle of the civil rights years, to think that there were in my hometown people who were dehumanizing other people because of the one-tenth of one percent difference between them is quite an awesome thing to contemplate.

So I would like to ask you, if you could say in ways that would make sense to us, explain to us a little bit what is it that makes us the same and what is it that makes us different? And how could we communicate this scientific knowledge to people in a way that would diminish the force of racism and other bigotry in the world in which we live?

DR. LANDER: No, but what a wonderful question and what an important thing. I even want to point out that when you speak about the one-tenth of a percent difference between two groups who might be warring with each other, there isn't a one-tenth of a percent difference between those groups.

DR. CERF: It's even less than that, isn't it?

DR. LANDER: In fact, the variation in the human population is really that ancient variation we had back a long time ago. Most genes come in about two or three flavors, two or three spelling differences. And those flavors of the genes weave themselves through the human population like a tapestry. You and I have one-tenth of a percent difference. But two ethnic groups don't have one-tenth of a percent difference. Most of the variation is not between groups, it's within the individuals within the group.

In fact, since we all left Africa 7,000 generations ago, there just hasn't been a lot of time to build up large amounts of genetic variation. We do see differences. In fact, we're cued into seeing differences between people. That's very misleading about what is really going on at the genetic level. You may think two humans look very different from each other, but the truth is they're much more genetically similar than two chimpanzees are. Chimps have much more genetic difference within their species than we do, because we are such a new, young, small species.

And so, in fact, there are not significant genetic differences between warring parties in most parts of the world. A geneticist going in could not find those differences. Indeed, it may help -- I don't want to be naive about that -- but it may help for folks to know that the differences that are out there are woven in every population. Maybe they're at slightly different frequencies, but they're throughout the whole population.

I don't imagine that will solve prejudice and that will solve racism, but, in fact, I don't see a scientific basis for drawing lines between people there.

DR. CERF: So you're saying that racism isn't a spelling error?

DR. LANDER: No, no, no.

DR. CERF: It's not anything as simple-minded as that at all.

DR. LANDER: Sure, there are genes that control differences in appearance and some of them have been selected over the years. But, in fact, they don't represent the majority of variation in the genome. And I, as a geneticist, and I think most of my colleagues appreciate that those are not the places to draw lines.

DR. CERF: So, therefore, that's not an excuse. That's wonderful.

DR. LANDER: No, I think the interesting variations that are the variations of things like the number of color receptor genes you have. Some folks have two red receptors or three red receptors, and do they see the world differently? There's a lot of wonderful texture of variation out there, but it's not a variation that ought to be dividing us.

MS. LOVELL: I'm going to bring this back to the Internet with Omar Wesso (phonetic). You started, as a youth, playing around with computers and now you're an Internet analyst and entrepreneur.

Q: Thank you. I wanted to ask, basically, we have seen numerous wonderful and unanticipated uses of information technology developed. You mentioned electronic commerce. I wonder, how can we encourage more young people and adults to move from being consumers of these future innovations to being creators?

DR. CERF: Actually, based on what the President observed, I'm not sure we have to encourage too much. I think that most of the innovation that's happening in my field is happening among young people between the ages of nine and 20. One of the sons of an FCC Commissioner is already teaching his third grade class how to make web pages. And I think -- don't look behind you, there is a 13-year-old gaining on you.

I honestly believe if you're looking to understand where the future of the net is going and all of this technologies, don't ask an old fart like me, go talk to the kids that are teenagers or in junior high school because they are the ones that are going to decide what things they want to buy, what services they want, what new products they're going to build, and a lot of them will do it themselves.

So in a funny way, I'm not sure that we have to work very hard to achieve the objectives you're suggesting. These kids have adopted the net, it's theirs. The one message I get from them is, this is our network, don't screw it up. (Laughter)

MS. LOVELL: Well, Mrs. Clinton, let's go to the Internet.

MRS. CLINTON: All right. This is one of the real joys of being able to have these evenings is to have questions that come in. And so, do we have a question that we can put on my screen? Do I have to -- Ellen, if it's on that screen, why don't you read it?

MS. LOVELL: Yes, that was supposed to happen. Well, here we go.

DR. CERF: By the magic of technology. (Laughter) That's it. How many engineers does it take to --

MS. LOVELL: Somebody just said one of the postcards got lost. (Laughter)

This is from Seattle, Washington, and it's to Vint Cerf, and it says: At our current pace, do you think we'll gradually lose our interpersonal skills and become more and more isolated from each other? Are we losing our tribal or village human experience, in exchange for a purely impersonal, technical one? Thank you, Uncle Dave. (Laughter)

DR. CERF: You know, this reminds me of the glass window syndrome. Whenever we get into an automobile and we start driving, we're isolated from the world by a sheet of glass. And boy, what does that do to change our behavior.

Well, I don't agree with the proposition that the Internet isolates, or dehumanizes, or separates us. I don't think it does any such thing. I think that it connects us in ways that we never could be connected before.

I see preservation of culture. I see the sharing of experience. I see the sharing and preservation of history in that medium. I discover people and places that I never would have discovered before, were it not for the spread of the net. And I think, frankly, the travel industry is going to benefit more than any other segment of the population, because people discover other people with common interests, that they otherwise could not have encountered. And then they want to go and meet them.

And so my guess is that the net is actually going to create a far greater, global conversation than we ever had before. And it will create virtual villages of people with shared interests that couldn't exist except in the world of cyberspace.

MS. LOVELL: Yumedas Chikas (phonetic) is a student from Wheaton High School who participated in the National Institute of Health pilot program, teaching genetic literacy so young people would be able to make informed choices in the future.

Q: Good evening. Both the Internet and genomics gather billions of pieces of data. Who owns information gathered about me? Is that information secure, in the database or on the Internet? Do I have a right to keep my information, including genetic information, private?

MS. LOVELL: That's really for both of you.

DR. CERF: I think you do. And it seems to me that it's no different than any other personal information that might be about your income, or your financial situation, or other personal activities. Of course, the problem is not the technology. And don't let anybody tell you that, well, the solution to this problem is cryptography. It's actually a powerful tool, and it's a good, useful tool to have.

But what is really at issue here is how we decide as a society to treat that information. How do companies and other organizations who obtain it in the normal course of work -- if it's medical transactions, medical treatment and things like that -- how do we decide, as a society, to treat that information?

And in my view, that information is just as private as anything else that we would consider personal information. But in order to protect it, we have to decide that's what we're going to do.

DR. LANDER: Now, Vint, you say he has a right to that. And that's because you recognize his right, but I don't know that at law we do recognize that right yet. I think, in fact, we have to go quite a ways to protect the right that we feel you should have to control your own genetic information.

Do you have a right, right now, to stop someone who takes your blood for a particular test, medical test, from doing 10 other tests to it? It's not at all clear in the law you do right now. Do you have the right to stop me from taking a cocktail napkin that you might have wiped your face with and do a DNA test on it? It's not clear you do right now.

I think, in fact, if we're going to make sure that you have an opportunity to seek genetic information for your own benefit, we're going to have to protect it. And I think we're going to have to protect it with a lot -- to recognize that right, to let you sue for that right and to make sure that everyone respects that right.

And I know there's a lot of effort to do that right now. And I think it's one of the most important remaining works to make sure that the Human Genome Project itself delivers a society that citizens can really use. And I really, for my part, endorse the efforts to pass such legislation. I really call on everyone to get to it.

DR. CERF: Could I ask for you -- we've got two very prominent --

DR. LANDER: Right. You guys have more to say about this than -- (Laughter)

THE PRESIDENT: Let me just say this. We've been working on this, and it's very important to me because I'm a fanatic about this issue. I want unlimited scientific discovery, and I want unlimited applications. But I think we don't want people to lose their sense of self and the fragility of their personhood here in some sort of assault. So we've been working on this.

What you said sounds great, but it's not as easy to do as it sounds. So I think it might be helpful, if I could just ask Secretary Shalala, who is in charge of one piece of this, which is our efforts to protect the privacy of medical records, just to talk a little bit in practical terms about what we're doing to respond to this young man's question.

Donna, would you -- there's a mike.

SECRETARY SHALALA: I think the most important thing I should say to this young man -- actually, the answer to his question is, it depends on what state he lives in whether his medical records --

But the one thing I can tell you is that there are more federal protections on your Blockbuster card than there are on your health information. And that is, no one can go to your local Blockbuster and ask what movies you rented because they're actually is a federal law that protects your Blockbuster record and the videos that you rent.

What we're trying to do is to set out a set of principles -- and we'll probably end up putting in place some regulations if Congress doesn't act. The President has been urging Congress to act. But the fundamental principle is that health care information ought to be used for health care purposes. And anyone that doesn't ought to be held accountable; that you ought to have the right to get access to your health records to make corrections, if necessary, but that there are larger public purposes.

The President cares deeply about research, for example, and that all of us have to agree as a society that our health records can be used for research purposes but, at the same time, protect our privacy.

So, we have to have a set of principles and the fundamental one is that health care information for health care purposes -- they can't be used to deny you a job or access to college or to deny you insurance.

THE PRESIDENT: But let's deal with two hard questions here, real quick -- I think this is important. Question number one, pretty soon if the genome project is brought to fruition, according to what Dr. Varmus has told me when I spent a day out there, it will become normal in the not too distant future for young mothers to go home with their babies from the hospital with a map of their genetic future. You may not want to know about Alzheimer's, but you could know about things that even if you can't cure you could delay, defer or minimize. So you get that.

Now, the mother and the father are employed by someone and they provide family health insurance. Since private insurance is based on a reasonable approximation of risk -- I don't agree with the way we finance health care in this country, you all know that. But that's a fight I didn't win here in the last seven years -- if it's based on an assessment of risk, what should the insurance company have a right to know? And if the insurance company doesn't have a right to know, haven't you undermined the whole basis of privately-funded insurance based on risk -- question one. Question two for you.

DR. CERF: We don't get to answer that one.

THE PRESIDENT: Yes, I want you to answer that, but I want you guys to talk. Question two: This is the problem we face in a much more grave sense in dealing with the prospect of cyberterrorism or something. It's one thing for us to write laws that protect privacy of records. But you just got through -- in answering Omar's question, you were talking about how, well, but all these kids are always figuring out -- well, among the things they're figuring out is how to break into various systems all the time. So even if we had perfect laws, how are we going to protect privacy when we're dealing with all of these creative geniuses out there working through the net? Respond to those two questions.

DR. CERF: Now, let's you and him fight. Okay.

DR. LANDER: No, no, it goes right to the heart of the problem here. At some level, is insurance about matching rates to risks, or is it about sharing risks that none of us chose? And what happens is that at the beginning where we don't know that much about our future, there's not so much tension between those two. As we learn more and more about specific risks -- that you might be at risk for cancer and someone else might be at risk for diabetes, we could make exclusions or put in special rates for your cancer risk there -- we can, in fact, tear apart the basis for pooling the risk and sharing the risk.

But I think the important point to recognize there is if one insurance company won't wish to forego that information when its competitors had that information -- well, it wouldn't do very well economically. But if all couldn't use that information, they wouldn't have any disadvantages relative to each other.

There is still the question -- what I guess economists call "adverse selection," people who know they need more insurance for some particular risk going out and buying more. But for some basal level of insurance, I think, in fact, we ought to have a way where some insurance package -- and we probably don't disagree much on this -- has to be available to people quite independent of those risks.

And maybe then, if you want to get an extra million dollar policy on some cancer thing, you might have to consent to it, because that's a different kind of economic bargain. But at some basal level, no, we've got to decide that we mean this is a social way to share risk; to say with respect to all the things that could happen to you, there but for the grace of God go I, and decide that that's the basis for our system. And I think we can by making sure that we uniformly don't use that across all companies, make an economically viable system that doesn't. But there's obviously a lot of work to be done, and I don't mean to over-simplify any of that.

You get the other half.

DR. CERF: I get the other half. Thank you. Okay, I want to come back to this question of privacy, though, but we'll do that afterwards. The question about how we protect ourselves against all those really smart kids out there is that some of them are helping us do that, in fact, already. (Laughter) But I don't want to understate the challenge that this poses.

You'll recall, Mr. President, that your Information Technology Advisory Committee not too long ago recommended that we increase the level of research and fundamental software principles that will allow us to build much more robust systems than we can today. There's a lot of very basic research that needs to be done to make software more reliable and more resilient. And that's not something that you just do on a weekend's work. It means serious and sustained effort in the computer science departments here and elsewhere to understand how to cope with the billions of pieces of software that are interacting in networks in these little slices of computing that are everywhere imbedded in the woodwork.

So the answer is, there's no easy solution to that. But it's not going to require a breakthrough of huge magnitude; it just takes some very sustained work. And we have to make sure that that work gets supported.

MS. LOVELL: You know, I think Carol Greider (phonetic) actually had the perfect follow-up question to the President's question. Carol is a geneticist with John Hopkins University, with an expertise in -- as you will see -- a very special interest in genetic information.

Q: To pick up the question that you raised yourself, a question of Dr. Lander, and that is that, given that a lot of different diseases have both a genetic component and an environmental component, and the genetic component may be made up of a number of different genes, what might be the advantage to parents knowing the complete genotype of their children as they go home, knowing that there are environmental as well as genetic influences?

DR. LANDER: Well, goodness, today, sending parents home with complete genome type information, even if we could do it, would overwhelm them -- would overwhelm them because they couldn't possibly digest that information; and because nobody could help them digest that information. Genes interact in a complex way in an interactive environment.

We're going to have to think very carefully about how to supply information that represents what we really know and what people can act on. There are going to be places where we can make a big difference. We know there are genetic predispositions to juvenile diabetes. We don't know quite how to prevent that, but there are strategies that people might use if you knew a child was going to be at high risk for juvenile diabetes. And that's something that you're probably have to do before the age of five, to intervene then. So a parent is going to have to know that information and do something about it and make a choice. And they may be strategies that you wouldn't apply to everyone in the general population because there is risk involved.

So, we're going to have to match the information to being able to act on that information and to the responsibilities of parents do it. I think the gaping hole right now is education. And I don't just mean that in the form of the American people don't know enough about genetics and they should pick up genetics text books. I mean that we don't know how to explain it. But a tremendous amount of research has to go on on how to communicate this in a way that people can hear and understand. It's easy to talk around statistics and nucleotides and things like that, but I don't think it connects for people.

And so I think we have a huge amount of work to do, every bit as important as the scientific work, to connect up with the general public and expectant mothers and fathers.

DR. CERF: Can I come back to one very interesting thing about this privacy question? Often, when we're trying to do scientific research, it's really valuable to have a pool of information about the health conditions of the entire population that we can deal with epidemiology and all these other things, we can see how certain treatments are doing in a large population.

Now, normally, the way we deal with this is we decouple the personal information, the identifying information, from the medical information. And that sort of works for almost all of the cases I can think of except genetic information, and here's why. The complete genetic sequence of a person is the most definitive fingerprint I can think of. It defines the person. So if complete genetic information is available to you and that's associated with any of the other medical information, somehow or other that's the ultimate fingerprint, you can't decouple the personal information because it is the personal information. So what are we going to do about that?

DR. LANDER: We're going to sign you up for the committees thinking about how, in fact, you parcel out that information in ways that we can still do research and still protect the privacy.

I think both are important. We default on being able to do research because of an undue fear that information will leak out, I think we will disadvantage people. If, on the other hand, we let that information leak out, we will also do a great disservice. And we're going to have to chart a course down the middle and it's going to take a combination of information scientists and genomicists to think about how to do that job, so we'll find out.

MS. LOVELL: And to get to some more of that information, I wanted to acknowledge Stephen J. Gould, the biologist who, as President of the Association for the Advancement of Science, helps the public fathom issues in science. Dr. Gould.

Q: I wanted to ask you two quick questions -- broad in implication. First of all, what is the human genome, given all that variation? Admittedly, not much between any two, but integrated over the genome, what's it going to look like when it's finished? Is every position going to be A, C, G, F, T; A, C, G, F, T?

Secondly, given the reductionistic traditions of the way we think in Western science, how are we going to get people to understand and recognize that that little CD of yours is not a human being, and that humanity and humanness is very different from the blueprint that's only a grand average of all of us -- never going to explain what makes a Yankee versus a Red Sox, which is arguably the most important question in America today. (Laughter)

DR. CERF: Certainly will be in the days ahead.

DR. LANDER: Oh, goodness. Well, the first one -- what is the human genome -- sort of a first-order approximation, it will be a list of As, Ts, Cs and Gs, just like you've got lists of ones and zeroes. And it will be an arbitrary sequence from one person -- actually, a harlequin of sequences from different people. And we won't fuss much over the one letter in a thousand.

As time goes on in the years ahead, each of those letters will get annotated to say, this is a spot of variation. This is a spot where you've got a gene that frequently comes in a couple of different forms. And that will get layered on and on. Every single nucleotide of the human genome does vary in somebody in the population, but the ones we're interested in are the common ones, where we might stand a chance of understanding medical significance.

With regard to the other question you ask -- how do we make sure that people don't get the view that the CD is the person -- I think that scientists have a real obligation in their choice of metaphors. I think metaphors are tremendously powerful things. We can call the human genome "the blueprint," the "Holy Grail," all sorts of things -- it's a parts list. It's a parts list. If I gave you the parts list for the Boeing 777, it's got 100,000 parts on it, but I don't think I could screw it together on the basis of that and I certainly wouldn't understand why it flew because of that, and I wouldn't understand all sorts of things because of that.

We've got to understand that the Human Genome Project is tremendously exciting, but it is a piece of infrastructure. It is infrastructure building like we build roads in this country, to help commerce. It is an infrastructure-building project like the Internet, which is not the information, but a backbone, and we've got to make people understand that despite all the wonderful, highfalutin talk about genomics, it is the beginning, not the end. And I don't expect to be able to read out human nature in that code, and I certainly don't see any evidence of anything distinguishing between Yankees fans and Red Sox fans.

DR. CERF: Could I just ask one question about this? It's always bothered me that people use the phrase "blueprint," for example, to describe the human genome or any genome. And I don't think I think of it that way and I'm hoping that you will agree. It really feels more like it's a program that gets interpreted, and you start out with one cell, and then it gets fertilized and then things start to happen. And it's that sequence and portions of it that get interpreted and produce proteins and create -- so it's more like executing a program and then having a result as opposed to simply being blueprint.

DR. LANDER: It's both the data and the program itself. But I've got to emphasize that when you get the CD, you don't know how to read the program any more than if you got a CD of ones and zeros for a whole bunch of computer programs written in a language that you couldn't understand.

DR. CERF: Or didn't know -- right.

DR. LANDER: -- or didn't know. And so, in fact, we're dealing with a language here that is three billion years old, and it's got patches and patches on the code by evolution. It's never been documented very carefully -- you think you've got problems with documentation -- (Laughter) -- this stuff hasn't been documented --

DR. CERF: Wait a minute -- is there a Y2K problem with the human genome? (Laughter)

DR. LANDER: No, no, I mean that quite seriously. If you have trouble sorting out Y2K problems in a piece of Fortran code written in the 1960s, just imagine the issues in trying to decipher the workings of software that's the product of 3 billion years.

DR. CERF: You know, I used to think we were going to get people angry at us for the Y10K problem, right, when they'll say, "why didn't those jerks 8,000 years ago fix it with an extra fifth digit?" Now, you're wondering why didn't that stupid bacterium -- (Laughter) -- three billion years ago -- why didn't you do it the other way?

MRS. CLINTON: I have to ask Stephen J. Gould, since he sort of alluded to this by raising the Red Sox and the Yankees, how would you answer the question about what genetics will tell us about behavior? Is a Red Sox or a Yankee fan bred in the DNA? What is it we're going to find out about behavior?

DR. GOULD: Certainly not. There is a basic human nature based on the very minor extent of the differences that Eric so well specified. But most of what interests us is the enormous cultural overlay, which is obviously permitted by our common genetic nature, but that's not a particularly informative statement. Thank goodness the richness of our differences in our cultures is not so specified, and is what is influenced is enormously flexible and that will preserve our diverse humanity and so biology will join culture and even give us some liberty, thereby.

MS. LOVELL: Mary Davidson. As executive director for the Alliance of Genetic Support Groups, you represent people with genetically based conditions.

Q: Yes. I have a question for you, Dr. Lander. I'm speaking from the perspective of families that look to genetics with such tremendous hope, but still with their eyes open for the undertow that we've been talking about. So let's put ourselves in a very personal position. Do I really want to know if I have a predisposition for a disease for which there is currently no medical treatment? And if I know that I'm already -- if I already know that I'm at risk for a disease, what happens to me and my family, then, in the lag time between obtaining this knowledge, having it on my medical record, and then a treatment certainly being developed in the, I hope, near future?

DR. CERF: Boy, science is a lot easier than policy, isn't it?

DR. LANDER: Yes. Your first question, do you want to know about genetic information concerning traits where you can't do anything today, at least where there's no treatment today -- well, in some cases you might. There might be instances -- for example, people with Huntington's disease or at risk for Huntington's disease may still want to know because it will affect their reproductive decisions, or may affect their reproductive decisions. And so there can be instances where that would be useful.

There may be instances where early screening might still be of some benefit -- you don't have very good treatments, but there might be purposes with regard to some cancers where early screening might be of value.

But now, if we can't do anything about it, on the whole it's not clear to me that that information really does anyone any good -- although I must say that if the person wants to know, they have every right to know. We're going to have -- as you point to -- this very uncomfortable lag period between when we can predict and when we can prevent, or cure.

It's going to vary tremendously. For some diseases, it might be a couple years, and for other diseases it could be a century, because we might not have a way to get into the right cell in the brain to be able to do something. We have to be honest about that.

Genetics holds tremendous promise, but it doesn't guarantee that understanding is a cure. It's just that ignorance is usually a tremendous obstacle to the possibility of a cure, and that's all that science can hold out.

We are going to have to help families get the information to make the choices about what they want to know. We clearly want to know it as scientists. We want to be able to race as quickly as possible to preventive therapy. But this is going to have to be a conversation, and a multi-textured conversation, because every genetic disease is different with regards to its risks, with regards to the people it affects -- young children or older people in life. That's why I think it's so important that we have a dialogue between scientists and the general public on this.

DR. CERF: Could I just find out something here? Now, I think about how difficult it is for us to understand the behavior of the Internet and all the computers that are on it, and all the software that's on it. And yet that system, in some ways, is not even as complex as the interactions that happen in our human bodies, as our bodies develop and as the DNA is interpreted. People sometimes must get the idea that this is like clockwork, and it isn't. We don't actually know what will happen. We know what might happen, but we don't know deeply exactly what will, and we can't predict it.

So people who get this genetic information and misunderstand it to be a prescription, a prediction, would be terribly misled. And, in fact, I don't even know if you can quantify how little we actually can say about what the outcomes are going to be. It's so complex.

DR. LANDER: But it varies for each disease --

DR. CERF: That's the point.

DR. LANDER: -- and in some cases we do know things. You know, we can't deny the fact that there are genes that confer a risk of early onset breast cancer. And we can statistically measure the population, and say with some statistical certainty, even if we don't know the whole circuitry of how it happens -- although a great deal of progress has been made on that -- that a young woman who's diagnosed -- who is told that she has a particular mutation has a particular risk in life.

Now, it may be that some environments will push it one way or the other, and we don't know enough about it, and that we're giving an overall average number to everybody. But that number's still very different than the background risk.

DR. CERF: Well, I understand that --

DR. LANDER: So we struggle our way up with very imperfect information. But it's valuable information.

DR. CERF: Are there cases where there isn't any doubt? In other words, a genetic mistake will absolutely, 100 percent, guarantee there's something broken? Can you give us some examples?

DR. LANDER: Many examples of that. Huntington's disease, that I alluded to briefly, has a virtually 100 percent penetrance -- the word we use for a probability of effect -- in the course of life. There are a handful of cases where it might be put off rather late. There are many relatively rare genetic diseases where a gene is just plain broken, and it's clear that every individual who inherits that broken copy or two broken copies from each parent, will indeed have that genetic condition. The tough cases are the ones -- the ills that afflict most of us: heart disease, diabetes --

DR. CERF: Okay, those have variations --

DR. LANDER: Those are the ones that are multifactorial, that do interact a great deal with environment. Those are the ones most people will be interested in in the long run, and those are the ones where we have the most work ahead to do. But there's the whole range, from certainties to things that, in fact, can be completely modified by environment.

Let me give you one small example. We test every child in America today for a genetic disease. It's called phenylketonuria. Babies are tested with a heel stick at birth to see if they have this rare genetic disorder called phenylketonuria. Those few babies that have it lack an enzyme for digesting a nutrient, phenylalanine. It happens to be in NutraSweet, so every Diet Coke can -- I saw the President drinking Diet Coke -- if you look on the side, it says, "Warning to phenylketonuric: contains phenylalanine." It's a genetic warning on your Diet Coke can.

DR. CERF: Oh, and you can't digest --

DR. LANDER: My point is, they can't digest that nutrient. And if they have it from birth, it will build up and poison their brain. And it's a 100 percent form of mental retardation -- except that if you know it, you can put them on low-phenylalanine diets from birth and they'll have normal intelligence. You've got there an instance where we've got something that's completely genetic, but, of course, it's completely changeable with environment. That's the range of complexity we're talking about.

DR. CERF: So let's follow up on that, if it's okay. What -- suppose we know this. We know that we've got that broken gene. Now, you said, let's change the diet to deal with the side effects.

DR. LANDER: As long as we're lucky, in this case, we could.

DR. CERF: Now, is there anything else that we might anticipate? Can you actually imagine genetic therapy that goes and does something that will correct the problem?

DR. LANDER: Sure. You can imagine pharmaceutical companies developing a small molecule, a drug, that tickled some other gene to make up for that deficit. And that actually happens. There are strategies like that. You can imagine gene therapies, where some kind of a viral vector restores the missing gene -- a clotting factor, for example, into some cells in the body.

There's a whole myriad of possibilities. The thing about the genome project is it gets you that basic information, but then it splays out in a hundred directions of possible therapies that we may have to do, and there's just a century of biomedical research that's going to have to follow on to be able to deliver on the possibilities for each of those.

DR. CERF: To draw the informatics and genomics together for a moment, we wouldn't be able to do some of these things if we didn't have the computing horsepower and the memory and the ability to share the information that we have now. That's fascinating.

DR. LANDER: Not a chance. That's right.

MRS. CLINTON: We have also with us Dr. Francis Collins, and I know you've thought a lot about this question about the gap between information and treatment. And I wanted to ask you what you thought.

DR. COLLINS: Well, it's an interesting discussion we're having. And I think from the perspective of individuals who currently suffer from some of these diseases, or they exist in their families, there's a great sense of impatience -- where are the cures, where are the end points to this very promising research? As a physician I'm very sympathetic with that.

I think what we're talking about here is working on a pathway towards the top of the mountain. The top of the mountain is curing diabetes, curing hypertension, curing cancer, curing schizophrenia. But to get to the top of the mountain you have to travel a certain path. The excitement we're talking about this evening is the genetics of genomics provides us with a path that we didn't have before. It's a very powerful way to get to the top of that mountain; but we shouldn't fool ourselves that by building this base camp called the human genome we're already up there and have solved all of those disorders. But it is the best way going right now to get to that point.

And there is already good news around us with some of the hills nearby beginning to be scaled. We talked about various examples. I put forward the example of colon cancer, where we now know how to identify the roughly half a million people in the United States that are very high risk for colon cancer. There is a circumstance where it's not a diet or a drug, it's surveillance.

If you know that you're in that category, you get your colonoscopy beginning at age 40 and do that every couple of years; you're going to find that polyp while it's still small enough to be removed, and you'll save that death from metastatic colon cancer, which is an awful one.

So there is a circumstance where the diagnosis itself can be life-saving. But to be honest, the diseases won't all be like that. And then we have to keep climbing up the mountain. And some of the things we'll find at the top of the mountain will be gene therapies and some of them will be drug therapies. And if you're a family with that disease, you don't care as long as it's one of those and as long as it works.

Cystic fibrosis was mentioned by Eric earlier on. I had the privilege of being part of the team that found that gene, and it's 10 years on and we haven't cured it yet. But, you know, there are now a dozen drugs in clinical trials for cystic fibrosis that have come about because we understand how the gene works. We wouldn't be at that point now if we hadn't had that basis, that foundation, that infrastructure of understanding the genetics of this disease, which was a total puzzle until 10 years ago.

So one should be both optimistic about where we're headed to and realistic about what the challenge involves and how much more medical research we need.

MS. LOVELL: Now, we are going to go back to the Internet, and it's for you, Mrs. Clinton.

MRS. CLINTON: This is a question from Danella Bryce (phonetic) from Sydney, Australia. And the question is: Obviously the power and the concept of the modern information technology is tremendous. The fact that I can sit here in my office in Sydney and send this question is a remarkable thing.

However, for the past 25 years, I have been working with poor communities in developing countries trying to assist them just to reach a reasonable, sustainable level of development. How can the new technologies which are such a powerful information tool be harnessed to assist in the global battle to alleviate the growing numbers of people living in very disadvantaged circumstances?

DR. CERF: Well, let's see. First of all --

THE PRESIDENT: Can I give -- you said that we got 6 billion people last night. Half of them live on $2 a day; 1.3 billion live on $1 a day or less. Those are the numbers behind what Ms. Bryce is asking.

DR. CERF: The first problem is that you can't take this technology and just put it someplace and expect it to solve all the problems that poverty and lack of infrastructure and lack of sanitation and lack of education and everything else visit upon us, so the beginning of all this is that you have to make investments in infrastructure in those countries where there isn't any in order to get them to the point where these new technologies can actually be of use.

There are pockets of times when the technology can be installed and used immediately. For example, in medical treatment -- in obtaining important information about economics and how to operate country, that information can be made available immediately, but in small places -- at university, within the administration. But for the general population, the first problem is getting them to the point where this technology actually is useful.

I can remember an effort at one time to send personal computers to Africa in the hope that somehow, this would help them leapfrog into the 21st century. Well, the first thing you discover is, there isn't any electrical power, or if there is, it's not very reliable. Then you discover that the physical housing available for where you put the equipment is leaky and rain comes in, and even more amazing, there are a lot of bugs that crawl around and they're not the software, they're the real kinds that crawl into the machines and they do funny things to the equipment.

So then you don't have enough people who are trained in order to maintain and operate the gear. So this -- it's not true that every country in the world that is still unable to take maximum advantage of this has to go through everything we can before they can get there, but there are some basic things that have to happen.

Just as a small example, the World Bank says that for every dollar invested in telecommunications infrastructure $3 of gross national product can be expected to arise from that. There are formulas like that that people can begin to work with, but believe me, this is a long, hard process.

A good piece of news is that all of the costs of this gear is dropping dramatically. You hear about the $200 computer. These are -- consumer prices, by our standards, they're still sky-high by the standards of countries that President Clinton mentioned. But the fact is, the technology is rapidly becoming less and less expensive.

Someday, Eric, we may actually be able to grow our computers because they'll be molecular in nature, and we'll use something very like a string of DNA to describe what's supposed to happen, and the thing will actually get created. So at some point, we'll be able to deliver these things at very low cost, but it's going to take another mountain to climb like the one we talked about earlier.

THE PRESIDENT: If I might just interject, I don't know the answer to this, but I've spent a lot of time thinking about it. This woman, Ms. Bryce, she works and she's talked about that she works in sustainable development. A big problem in poor countries, they totally destroy the environment to try to develop and then they don't have anything upon which to develop. The biggest problem in our hemisphere is Haiti -- if you fly over the island of Hispaniola you know when you're going from the Dominican Republic to Haiti because in all the years when it was governed by dictatorships they just tore down all the trees and -- if any of you know anything about it, know this.

The real question is, we used to have certain assumptions about development in a poor country; that if you wanted ever to build a middle class life for a substantial number of the people, yet have X amount of electric generating capacity, and you had to have Y number of roads, and you had to have Z number of manufacturing companies, no matter what they did to greenhouse gases, and that eventually you get around to building schools and universal education -- and then 30 or 40 years later you start letting the girls go to school with the boys and there is this sort of thing that would happen.

I do believe that the question, the real question is if you're running a country like this, should you put this sort of infrastructure development first? That is assuming you've got a base level of electricity necessary to run a system. Should you do this first because this gives you the possibility to skip a whole generation of development that would otherwise take 30 years in the economy and in education. And I think the answer to that at least is, maybe. That I think is really the question that this woman is asking.

DR. CERF: I have an example. A few weeks ago I got an e-mail, and the e-mail was an offer to do work. Basically, it said if you have web pages that you want to have formatted and put on a web site, for $125 I'll do 10 of these pages. Send me a Microsoft word file or a text file -- and, oh, by the way, if you don't have a Web site, for $250 a year I'll provide that for you, as well. This was signed by a guy in Bangalore, India.

Now, I was very impressed when I read that because this guy had figured out how to virtually export the talent in the country -- graduates of the Indian Institute of Technology -- to do work and to bring in hard currency into India from outside. And so that notion of being able to outfit a population with the ability to work not only locally, but elsewhere in the world through the net, is a very appealing one. I find it's taking hold in other places -- in Ireland, in Scotland, in Costa Rica, in Israel, in South Africa, and in Russia, where there are programmers working for Sun Microsystems, exporting their results through the net. So I think the maybe -- it may be even a little stronger than that. We'll have to see how this turns out.

THE PRESIDENT: If I could just give you one example, because I think this may have also relevance for remote, physically remote areas in America -- Appalachia, the Native American reservations, things of this kind.

We were talking before we came in here tonight -- I was out in northern California the weekend before last. And I was talking with a lot of people who work for E-Bay, and they were telling me that there are now, in addition to the employees of E-Bay, over 20,000 people who make a living on E-Bay, buying and selling and trading -- and that a fair number of these people were actually people who once were on welfare, who moved from welfare to work. That is, from -- and presumably a lot of them work -- didn't have a lot of formal education. They had made this jump, and a market had been created for them, where they lived, that otherwise would be alien to their own experience. They wouldn't have been able to go down to the bank and get a loan, and on and on and on.

Now, last year we made -- and this year we will make, through our aid programs in foreign countries -- over 2 million microenterprise loans to poor people, to help them start their businesses in Africa, and Latin America, and Asia. If you could somehow marry the microenterprise concept to setting the infrastructure of the Internet out there, I do think it's quite possible that you could skip a generation in economic development in a way that would reinforce rather than undermine the environment.

DR. CERF: The operative word here is "infrastructure." And you do have to have a certain minimum amount of it in order to make this stuff function reliably. And, of course, it has to be reliable, or you can't make a living out of it.

MS. LOVELL: Well, this is the perfect jump to Dr. Vanessa Gamble's question. She's from the Center for the Study of Race and Ethnicity at the University of Wisconsin. And as someone who worked to right the wrongs of the original Tuskegee study, I know you have a very special concern for access and for fairness.

Q: This is a follow-up question that goes into inequities. We've talked about some of the benefits of these technologies. And I think the question we have now is about the inequities and lack of access not just around the world, but in our own country. And how do we make sure that as we move forward, that all communities in this country are involved in the debates, and also get the benefits of these new technologies -- that you've talked about the benefits, to make sure everyone is included?

MS. LOVELL: That's really for both of you.

DR. CERF: Well, here we go -- two things. First of all, it's been possible to make things like Internet accessible in places where it hasn't normally been available, or it's not affordable, by putting it into public institutions, into publicly accessible kiosks and things of that kind -- in libraries, in schools. There's a major program, as you know, that has been undertaken called NetDay, to try to wire various of the schools up and provide them with access to the system.

We have to pay attention, just like Andrew Carnegie did 100 years ago, to making these facilities accessible to everyone who wishes to take advantage of them. And I remind you again of the horse to water; not everyone is willing to take advantage of these things. But where they will, we should make them accessible.

The other good news is that the cost of doing these things is dropping very rapidly. Not only is the cost of the equipment dropping, but the cost of telecommunications as well. And so, as time goes on, these things will become more and more in the reach of everyone. That's been true of most of the advances in technology that I can think of. In my own lifetime, color television -- which used to cost $1,000 in 1950 -- is a lot less expensive now, in today's dollars, than it was in the equivalent dollars 10, 20 or 30 years ago.

So that's a simplistic answer, and I'm not trying to argue that that's all there is to it. But the fact is that the thrust of all this is actually in our favor. The costs are coming down, and making things much more accessible than they would otherwise be.

THE PRESIDENT: Did you say you expected the penetration of the Internet to equal that of the telephone by 2006?

DR. CERF: It will exceed the penetration -- now, not necessarily -- it will be the same size as the telephone system by 2006. But I believe Internet will actually penetrate more deeply than the telephone or the television have. And the reason is those little tiny chips that I showed you a picture of before, they will penetrate into products that people just buy without thinking about them being computers. They're simply devices that do things for you.

THE PRESIDENT: I want to get to the genes, but I think we should answer that question, too. This whole question of whether we're going to develop a digital divide in our country I think is a very, very serious one. Our administration, especially the Vice President, when we rewrote the Telecommunications Act, we fought very hard not only to get people to participate in NetDay to hook up every classroom and library to the Internet by the year 2000 -- I think we'll get there by the end of the year; functionally, we'll be just about there -- but also, to get the Federal Communications Commission to adopt an E-rate which would subsidize the cost to poor schools and poorer hospitals in poor areas and isolated rural areas, so that everyone could have access in the schools.

Now, but the divide won't be bridged until the parents of those children have that in their home. So I think we ought to have as a goal at least to make access to computer technology and to the Internet as universal as telephone access is. And I think until we achieve that, there will be a digital divide, so we ought to try to hasten that day and promote whatever policies we can afford or we can achieve to hasten that day, because until we do, there will be a digital divide.

DR. CERF: I agree with that. In fact, it's a goal, a personal goal of mine, is to see, literally, Internet everywhere.

THE PRESIDENT: Now, what about the gene? That goes to patenting and all that, doesn't it?

DR. LANDER: Well, I think in a sense, the different communities and how they're going to be affected by this and what access they really have is much less with respect to genetics as a question of technology or infrastructure or cost than it is a question of understanding and education. I think, in fact, those whole genetic technology can look exceedingly complicated. And in its detail for each disease, it is very complicated. You've really got to know.

But there is a level of basic understanding about genetics and the choices and a few examples that everyone ought to know, because you can use them as reference points, as touchstones, for the other choices to come ahead. And I think every community, every ethnic community, every state, all of the different types of communities we have in this country ought to be having conversations about those basic fundamental choices, those basic fundamental examples, because as problems come up, we're going to need to refer back to them.

In a sense, it's easier than your problem. I don't have to wire up everything. In a sense, it's harder, because we have to penetrate people's understanding and their consciousness. We've got to get the different perspectives of different communities on the sorts of choices we're going to have. And different communities -- and I know your work, particularly with regard to examples in the African American community where, in fact, failing to pay attention to that really was quite a mistake. We've got to get that conversation going. I think, in fact, we can afford to do that, but it's going to take very active work to make sure we do do that.

DR. CERF: You know, the good news is that we have shown in the last 20 years that we can affect people's behavior, right? Look at smoking. Look at eating habits.

DR. LANDER: We should have done better on smoking.

DR. CERF: The point is that -- I mean, you can't smoke in the restaurants anymore, right? I mean, you can't smoke on an airplane. So we've managed to get people to pay attention to things that are important, and it seems to me we can do the same in matters related to genetics.

DR. LANDER: But we've got to understand how it is that -- we can't just get them to pay attention; we've got to understand how it's going to make a difference in their lives. We've got to listen, also. And it's that back and forth that we've really got to be doing.

DR. CERF: Amen to that.

MRS. CLINTON: You know, one of the issues that your question, though, raises, which is a larger one, is how this conversation that we're having tonight gets translated into decision-making at levels of government and within the private sector as well as the public. And it does strike me that there are some issues that have to be addressed now, even though we don't know the full implications of what's going to happen later. And how we create a climate in which what happens to your genome is as important as what happens to your taxes -- (Laughter) -- is a very challenging question.

And the President said something that -- he used the word "patent" -- there's a big debate about who will own this information and how will that information be used. Because in order to have the kind of openness of discussion that can lead to creating a climate that would influence decisions, there has to be a lot of give-and-take, and people have to have some interest in creating awareness among the public and not hoarding information.

So what do you say to the question about, well, what's going to happen to this genome information? Is it going to be the proprietary information of certain companies that then will be able to basically control information about it and the use of it, or not? And, if that's an open question, what do people in positions like the President and others sitting in this room have to begin doing to make sure that we keep the climate open enough so that when decisions have to be made we're able to do it?

DR. LANDER: I think there are two answers to that. One, it's unambiguously the case that information about the human genome has to be freely available to everyone in the world, to scientists, to non-scientists. It has to be viewed as a public right to have that information.

Now, we can guarantee that right. The way we guarantee that right is we, as a country, pay to get that information and put it in the public domain. That is, indeed, our policy now and we're doing it. I don't for a moment say that companies also shouldn't be gathering that information and doing good things with it because, in fact, they need to do that in order to deliver on the promise of cures and therapies.

But the core information at the heart of the genome, the genes, the variation, the circuitry ought to be out on the Web for all to see -- for all these nine-year-olds who are going to be inventing new genetic circuits. We can guarantee that.

We do have a question about patents. Patents are a separate question, of course, than access to information. In essence, to get a patent, you do have to disclose your invention. So the second question is, what's the state of patent policy and are there issues there? Well, yes, I think there are. It is important to say that there is a role for patenting.

If a pharmaceutical company wishes to develop a drug and invest $100 million to do so, it sure wants to know that when it comes to market, its competitor can't free ride on the clinical trials they did and bring the same drug to market. So we clearly need to be able to allow patents on some things to protect intellectual property and investment.

But I do think we're creating a thicket of patents right now. We're giving out patents willy-nilly for very, very slight investments. And I think in the long run that's a big mistake. In the 1800s, when you wanted to get land in the Homestead Act you had to work it for a while, you really had to do something important -- you couldn't just walk the boundaries and go file a claim.

What we have a situation right now is we have generic invention. You can discover all sorts of things pretty easily by computer and our patent policy hasn't yet caught up with that. And I think we are giving patents away and -- sort of a social contract -- we incent inventors to invent by giving them monopolies. But then we, as society, ought to get a good deal for that, and so we want to be certain that we set the bar high enough.

And I think that's actually an important thing, if I can say to people in a position to do something about it, to go back and look at our patent policy and ask whether this kind of generic discovery, generic invention really ought to meet the standard -- because I think it will create a set of boundaries and fences that are going to make it hard in the decades ahead for a pharmaceutical company that really wants to put the hard work into finding a therapy and a cure to operate, because they're constantly going to be bouncing up against boundaries of intellectual property.

So, I think it's not an absolute question. There's a role for intellectual property. But it is one of a degree and I, for one, think we're a little bit off on that and it would bear some thinking.

MS. LOVELL: I think, actually, Arthur Holden has a good follow-up question on that. He's the CEO of the newly formed SNIP consortium. That is a group of 10 pharmaceutical companies that will be posting their research in the public domain, as the government is doing.

Q: Very much a complementary activity to the public activities that are going on. Let me build on Francis's analogy of a base camp. We've essentially -- in completion of the sequence of the human genome we've created a base camp. And with that, as we've alluded to in the dialogue, a whole series of potentially fairly important questions. What are the few critical questions you think as over the next few years we get this base camp established, how should we begin to move up that mountain, number one. And, number two, the collaboration between the public and the private sector, which has been so critical in establishing that base camp -- how do you see that changing?

DR. LANDER: Two good questions. With regard to the information to come, the work to be done -- when we have that basic description of all the letters of the human genome there's a huge amount of work to be done. And I think it's going to look something like this. You've got to run through those letters and figure out where the genes are. That's not so trivial to do. We've got little bits, but no more than you can figure out exactly where one program starts and stops if you don't know the computer language, can we figure out where the genes are.

We have tricks for doing that and a lot of progress has been made, but we'll be using all sorts of things like sequencing other organisms. It turns out if you line up the human and the mouse sequence, almost all the genes have been conserved. The mouse also has 3 billion letters of genetic information and 100,000 genes. We are, in fact, not that different from mice, if you think about it -- (Laughter) -- in terms of body plan. We've got all the same organs that pretty much has got to have the same instructions, and it does. When you look at the genetic code our best way to find out how it functions is you line up the human sequence, the mouse sequence, and you look at what bits match. And that's the stuff that matters.

About 4 or 5 percent of your genetic code matters a great deal. Evolution has conserved it, and we can pick out the coding regions and the regulatory regions. And it's at the core of all genetic research today.

I say this advisedly because, at the same time, Kansas thinks evolution is such a shaky theory we shouldn't even mention it in the curriculum -- (Laughter) -- and it's at the core of what we're doing to try to figure out how to understand how the genome works.

Second off, we're going to take movies of how all the genes work. These detectors I briefly showed of how the genes turn on and off and different cells and different diseases, they'll be classifications of every tumor. There are already projects to do things like that. Classifications of what happens when a cell develops, when an organism develops. And all that data showing up on the Web already -- people are writing programs to figure out how it all interacts and pick up the regulatory regions. We're going to annotate those genes by the common variants in the population and all of that is public data that needs to be out there.

At the same time, take any one disease, and the work needed to produce a therapy or a cure is monumental. It is going to require private investment. It's going to require the possibility of profit on that. And so I'm pleased to see things like this consortium that are pre-competitive efforts of industry to try to lay that common infrastructure, and the role for the private sector in this is to take particular targets and deliver on them in a way that, as a public effort, we can't possibly do.

DR. CERF: Once we know, for example -- there is this little transparent worm called synarabditis elegans. (phonetic)

DR. LANDER: Bob Waterston, over there, was responsible in large part for the sequence of that organism.

DR. CERF: Okay, so now -- thank you. Once we now have the sequence -- (Laughter) -- now we have the sequence of this little half-inch organism, and now is it possible for us to actually watch how that sequence of genes gets interpreted so we can understand the complete development of that little worm? And if we know that, how does that help us with the bigger problem of understanding development in the human --

DR. LANDER: The answer in short is, yes, for the most part. we can know all the genes, we can figure out in what part of the body they're expressed. It takes work to do that. We can figure out under what circumstances they turn on and off. All of that gets us a kind of a program for how the worm works. And that's the work of another two decades ahead, but it's clear how that's going to happen. But how does it help us? It helps us in a remarkable way.

You see, the shock of genomics is this point about evolution. The same genes that lay out body plans in, for example, a fruit fly, or the genes that lay out the body plan in the developing human embryo, in fact, we look very different. but that same set of genes were invented about half a billion years ago, and they've been used and reused to do the same thing.

Now, if you want to understand birth defects, go do it in a manipulable system like fruit flies, or go look at the way that different pathways of signaling in the development of that clear worm you referred to work, because there are pathways of signaling in that worm that are the same as the pathways of signaling in human cancer cells.

DR. CERF: See, now this is starting to get really cool. Is it possible -- (Laughter) --

DR. LANDER: We think so. This is good stuff.

DR. CERF: Have I got enough computing power so I could simulate that whole thing?

DR. LANDER: No.

DR. CERF: No? You want to bet? (Laughter)

DR. LANDER: Okay, you've got a deal.

DR. CERF: I've got a bet. Okay, we've got a bet. We're going to work on this one. (Laughter)

DR. LANDER: We'll get back to you on this one. (Laughter)

DR. CERF: I mean, that could really be something if we could simulate the whole thing.

MRS. CLINTON: You mentioned one of the words that I think is in people's minds when they hope about what can come from this, and that's cancer. And we have somebody with us who has committed his life and his career to understanding and working on issues like that, and that's Harold Varmus, who is the outgoing head of NIH, and has been for the last six years -- and I think, by unanimous agreement, has done a superb job.

And I wanted to ask Dr. Varmus -- you know, we've committed huge resources to trying to find a cure for cancer, and there certainly has been progress that's been made. But what major gains lie in the near future, and how will the Human Genome Project get us closer to a cure?

DR. VARMUS: I assume by "outgoing" you meant I'm leaving, as opposed to my social behavior. (Laughter)

THE PRESIDENT: You mean, as if an outgoing head of NIH were an oxymoron? (Laughter and applause)

DR. VARMUS: Let me take this back to the direction you intended to go. (Laughter)

Well, indeed, the genome project is going to affect our approach to many different kinds of diseases. But you've heard the word cancer appear many times tonight. And let me explain why that is.

Cancer is essentially a genetic disease. And by that I mean not that it's simply oftentimes inherited, but it's a disease that results from accumulation of genetic variation. Some of that variation may be, in some cases, inherited. But much of it occurs during our lives when -- during the natural division of cells, mistakes occur, or cells are exposed to environmental agents that cause genetic damage we refer to as mutations or variation, and it's an accumulation of those changes that results in the alterations of normal cell behavior to cancer cell behavior.

The constellation of changes that occur in the different types of cells give rise to lung cancer and pancreatic cancer and breast cancer and others, varies from organ to organ, and it may even vary within one tumor type and another -- that is, within a single tumor type. Knowing which genes are affected, what the actual variations are, how those variations change the pattern of expression that Eric referred to that we can now visualize by putting all the genes on the chip and looking at the patterns of expression, revolutionizing every aspect of our approach to cancer.

We're now in a position to evaluate individual susceptibility to a number of cancers. Francis referred to one example, colon cancer, but many other examples exist in the skin, breast and elsewhere.

Secondly, we have options for much better definition of cancer. Cancer that may look the same -- two cancers that may look the same to a pathologist may look very different to someone who manipulates genes and looks at the patterns of expression. We now know that making those kinds of assessments can actually predict the right kind of therapy to use and predict the likelihood of a favorable or unfavorable outcome.

Finally, knowing which genes are affected is changing our approaches to designing preventive and therapeutic strategies. This is something which is going to come to fruition over the next 20 or 30 years, but already we're seeing harbingers of good news. There are therapies for breast cancer, for example, which are based on our knowledge of the few genes we already have in hand that we know to be important in cancer, knowing something about the kinds of proteins those genes make, what those proteins do, where they are positioned on cells. And it's this kind of tremendous bounty of information that's going to come from the genome project when we know all genes and know about their mutations and know about the behaviors of the proteins they make, which, in combination with the kind of information technology that is now available, will create a new world in cancer.

Now, this doesn't come without a cost. Some of the costs have been alluded to with respect to privacy and protection against discrimination. The investment we've got to make as a nation and a world to achieve these goals and very importantly, to refer to the issue of equity that was mentioned before, some of these things are going to cost a lot of money. We have to protect our citizens so that all are beneficiaries of the research and the products of research the nation has invested in it.

MRS. CLINTON: Dr. Varmus, is it likely that we will find out that every one of us is susceptible to something?

DR. VARMUS: Absolutely. We're talking about risks and there are relative risks. Eric mentioned a couple of diseases that we know are almost inevitable given a certain variation in the genetic code. But the vast majority of diseases that you and I are heir to are going to be contributed to by a large number of variations.

Even the cancers that we now understand to be influenced by inherited mutations are likely of different frequencies in different people, because of our environmental exposures and because of other genes that we've inherited that modify the effects of those central players.

So, this is very complicated stuff. And because we do have -- I mean, Eric and I may look somewhat similar, but we probably have 3 million differences between us. Some of those differences don't amount to a hill of beans, because they're differences that are in DNA that doesn't matter very much --junk DNA. But some of those differences are quite important. And some of them are going to make him more likely than me to have one set of diseases, and me another set.

It's going to be a long time before we have enough information to say what real risks accrue to each of us, but no doubt that -- this gets back to the insurance problem. And I agree entirely with Eric, that we should think of insurance as a way of providing pooled protection for the population, and not a system that is based on a gaining that allows individuals to seek the genetic information and then provide special protection for themselves based on that information.

THE PRESIDENT: Before we go on, I just want to say -- we sort of glided over this -- this man has done a magnificent job at the NIH for a long time, and I am very grateful. Thank you for that, for your service. (Applause)

MRS. CLINTON: I think we have time for one last question from the Internet, and this is from Kristin Janger (phonetic) from Vienna, Virginia. And the question is: What are some potential commercial applications or products that may emerge from advances in information technology and genetic research?

DR. CHEF: Together? Together? Wow. Well, some obvious ones, right? We've already touched on them. The ability to understand how the genome works allows us to simulate a lot of the therapies that we otherwise would have to test in more primitive ways.

And so, Eric, I would pose for discussion the possibility of being able to analyze and design therapies based on enough computing power to simulate what the effects would be. It's sort of like dry chemistry in a way. Is that a reasonable thing to consider?

DR. LANDER: Well, not only is it reasonable, it's happening. So when I gave you a hard time about being able to simulate the whole organism, well, that's a very complicated problem there, but there is a tremendous amount of work already, trying to simulate little bits and pieces of it to understand when we're not dealing with genes that are completely broken, but ones that might be just twofold down-regulated and we'd like to goose it up -- whether or not that would be a good idea or a bad idea. Because there are all sorts of feedback loops. That's the thing about the body, it's a very complicated, homeostatic feedback mechanism.

So, there's a lot of computer modeling going on already to try to understand what are the sensitive points to intervene at. Does it make any sense to make a drug against this step of a pathway, or will the body, in fact, regulate to that? What are the points that are really vulnerable and efficacious to intervention? We're going to need a lot of computer modeling because you get very surprising answers when you look at the whole system functioning together, rather than individual parts alone.

DR. CERF: So, now, it's occasionally tempting to fall into the trap of thinking of therapies that are genetic in nature. And I'm going to argue that, in fact, there's a much broader set of opportunities here.

This is all about understanding. It's all about depth of knowledge about how the body works. If we understand that well enough, then we can intervene in various ways that may be rather mechanical. For example, someone who has diabetes, we can actually sense the sugar levels in the blood. We can build little machines -- these already exist. These are devices that measure what the current state of sugar intensity is, and delivers a dose of insulin as needed -- rather than having to take a shot once or twice or three times a day. So there must be a bunch of things like that --

DR. LANDER: You said the key word. It's understanding. The reason we have public investment, the reason why science has progressed so tremendously in the past decades is that we have common public investment and understanding. The more we understand the process, the more we can then set it free to lots of creative forces in industry and academia everywhere to fix it.

The understanding, though, is a public good. It's a public knowledge. And that's what we have to keep investing in. And I think the one thing we can never slip into is thinking that because we've reached this particular milestone, the human genome --

DR. CERF: That we're done.

DR. LANDER: -- that we're done with understanding at all. There is a tremendous need for this continual reinvestment, by the public -- and I've got to say, the American people have been spectacular in investing, recognizing that this is one of our best public investments. And we've got to keep that up.

DR. CERF: Actually, this particular project is a wonderful example of the combining of informatics and genomics. The placement of all of that genetic information in one database, where it's accessible over the net, means that any researcher who finds a fragment of information can go to that database and find out if anyone else knows anything about that particular sequence. Is this a pattern that's been seen before, and if so, where, and what does it mean?

And that wouldn't have worked if we didn't have the ability to hold all that data in one place and process it. So now what we've got is a rapidly increasing rate of discovery -- because every time someone contributes something to that database, in a sense it interacts with every other piece of information in the database, and allows us to uncover the secrets much more quickly.

MS. LOVELL: I think you just summed up the whole evening. And I'm going to give the President the last minute.

THE PRESIDENT: Well, you know, that great humorist Ogden Nash once said, progress may be all right, but it's really gone on too long. (Laughter) And I was thinking that if he were here tonight, he would have to revise his opinion.

This has been an astonishing evening for me, and for Hillary, and I hope for all the American people and the people throughout the world who have been a part of this.

I want to thank you both. I want to just leave you with one thought: There are public responsibilities involved here, particularly for basic research. We have been very successful, and never more successful, than under the leadership of Dr. Varmus, in getting strong bipartisan, non-partisan support for investments in health. And I think that it's obvious that we can all see that as in our self-interest and as in the public interest.

We want to live forever, and we're getting there. But I think it's quite important also not to forget our responsibilities for basic research in other areas as well. And one of the things that we will come to know as the intersection of your two disciplines, informatics and genomics, come together, then we will have to study even more closely how all this that we know about the human body and its development interacts with changes in the environment.

So, other areas of research will be also important, into things like global warming and climate change and the sustainability of the environment. And what I hope we can do is to build a broader consensus, as we look into the new millennium, for the whole research enterprise in those areas where it will never be productive in the beginning, or profitable for people like you, to do the beginning. And then we can find these things, and then the American entrepreneurial genius will take off.

And so, I leave here with a renewed commitment to trying to help people like you get started. We may not understand it, those of us in politics, but we have an obligation to help you find it.

And when the first mouse graduates from Princeton, I will invite you both to deliver the commencement address. (Laughter)